In vivo translocation and down-regulation of protein kinase C following intraventricular administration of tetanus toxin.
A single intraventricular injection into adult rats of 100 mouse lethal doses of tetanus toxin (TeTox) produces a marked intracellular redistribution of Ca2+/phosphatidylserine (PtdSer)-dependent protein kinase C (PKC) activity. Changes are particularly pronounced in hypothalamus, hippocampus, and spinal cord structures. Translocation of PKC from the inactive cytosolic compartment to a membrane-bound active form is followed by a time-dependent reduction in both total activity and enzyme protein. The down-regulation of PKC activity in the hypothalamus is accompanied by a marked increase in a Ca2+/PtdSer-independent kinase activity, predominantly in the cytosolic fraction. Our data identify PKC as a possible indirect target for TeTox and suggest that down-regulation of the enzyme may provide a clue for tetanus neurotoxicity.
Aguilera
J
J
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Yavin
E
E
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D009928:Organ Specificity; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000494:pharmacology*
D013744:Tetanus Toxin; D011493:Protein Kinase C